The mosaic dataset it self can not be served directly from S3. You need to put it on a machine that is local to the server machine or use RDS. A common approach is to store the Mosaic dataset on S3 and then have a script that downloads the mosaic dataset to a local drive on the machines as part of an install script that can be run as part of an autoscaling group. Your question may be more about if the raster data can be stored in S3, which is a much more common requirement. This can be done using Raster Proxies. These are small files that are stored locally to the server but reference the rasters stored on S3. If moving data to S3 you need to consider the format and structure of the data to enable faster access. For more information see https://github.com/Esri/OptimizeRasters

There you”ll find how to store rasters that are used by a mosaic on S3. The mrf dataformat as an intermediate (proxy) between your files and your server are very powerful. Including local caching if you want